The Vertebrate Embryology Section seeks to elucidate molecular and cellular events that drive gastrulation. During vertebrate gastrulation, embryos undergo dramatic morphogenesis, beginning as a simple assembly of homogenous cells, and emerging as highly diversified beings with a recognizable vertebrate body plan. Errors during gastrulation, due to genetic mutations or environmental insults, can lead to developmental deformities or miscarriage. A more precise understanding of gastrulation will enable the development of diagnostic and therapeutic tools for human developmental disorders. Molecular and genetic studies have unveiled several signaling pathways that act in concert during gastrulation. The Nodal signaling pathway is an important example. Nodal-related proteins are a subclass of TGF-beta-related ligands that are unique to chordates. Nodal, the founding member of this subclass, was discovered as a gene essential for mesoderm formation in mice. Dr. Feldman and colleagues subsequently demonstrated that Nodal-related signals are also essential for endoderm formation and are key components of the dorsal gastrula (Spemann-Mangold) organizer. Supporting an evolutionarily conserved importance for Nodal-related signaling, Dr. Erich Roessler (Medical Genetics Branch), Dr. Maximilian Muenke (Medical Genetics Branch) and others have shown that mutations in Nodal signaling pathway genes can cause developmental anomalies in humans, namely holoprosencephaly and laterality defects. Analogous phenotypes are observed in zebrafish harboring Nodal-pathway mutations. Using the zebrafish as a model organism, we have three areas of research: 1. To gain a more complete understanding of the Nodal signaling pathway, we are seeking to identify molecules that control the delivery of Nodal-related signals to target cells, as well as molecules that elicit cytoskeletal rearrangements in activated target cells. 2. To obtain a thorough and unbiased picture of the mechanics of gastrulation, we are developing genomic approaches to profile regional differences in the gene and protein expression of gastrulating embryos. 3. Finally, in collaboration with the Muenke laboratory, we are using zebrafish embryos to test the function of human genes that may have roles in holoprosencephaly and forebrain development.